The anti-tumor agent, L-asparaginase, has precipitated diabetes mellitus in previously non-diabetic patients. Since the hyperglycemia in these patients was associated with hypo-insulinemia, an L-asparaginase induced blockade of insulin biosynthesis was postulated as a cause of this observation. An equally possible explanation, however, would be that L-asparaginase inhibits insulin release. The purpose of this study is to determine whether the diabetogenic action of L-asparaginase is related to inhibition of insulin biosynthesis, release or both. New Zealand white rabbits will be rendered diabetic by the intravenous injection of E. coli L-asparaginase. Random serum glucose and insulin levels will be measured daily. Groups of experimental animals and control animals will be sacrificed and the pancreata will be extracted for insulin. Collagenase isolated islets will also be obtained from control and experimental animals to determine the effect of in vivo L-asparaginase administration on in vitro islet function. Islets from control animals will also be exposed to L-asparaginase in vitro to determine an acute effect of L-asparaginase on insulin release. Similar studies will be performed utilizing the isolated, perfused pancreata of diabetic and control animals. Finally, the effect of L-asparaginase on insulin biosynthesis will be studied utilizing isolated islets from control and diabetic animals as well as control islets acutely exposed to L-asparaginase in vitro.